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The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.
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The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
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After cellular or tissue damage, the resident stem cells present in the human body can locally repair and regenerate the damaged tissue or organ. However, even though some tissues do not have stem cells, they can repair and regenerate with the help of pre-existing cells. For example, beta cells of the pancreas and hepatocytes of the liver can divide to renew and regenerate the tissue. Here, both cell division and cell death are well regulated by homeostasis.
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Stem cells are undifferentiated cells with extensive self-renewal properties that help them maintain their population during the fetal and adult stages of life. They can specialize in all cell types of the human body. However, their differential potential may vary and can be classified into five types. Stem cells can be (1) Totipotent, (2) Pluripotent, (3) Multipotent, (4) Oligopotent, and (5) Unipotent. Each stem cell has a specific origin; the fertilized egg or zygote is a totipotent cell and...
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Stem cell research aims to find ways to use stem cells to regenerate and repair cellular damage. Over time, most adult cells undergo the wear and tear of aging and lose their ability to divide and repair themselves. Stem cells do not display a particular morphology or function. Adult stem cells, which exist as a small subset of cells in most tissues, keep dividing and can differentiate into a number of specialized cells generally formed by that tissue. These cells enable the body to renew and...
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Efficient Differentiation of Human Pluripotent Stem Cells into Liver Cells
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The plastic liver: differentiated cells, stem cells, every cell?

Christopher J Hindley, Gianmarco Mastrogiovanni, Meritxell Huch

    The Journal of Clinical Investigation
    |November 18, 2014
    PubMed
    Summary

    Liver regeneration is complex. Transplanted hepatic stellate cells can contribute to the oval cell response, suggesting mesenchymal cells can act as liver progenitors. This highlights liver plasticity.

    Area of Science:

    • Hepatology
    • Stem Cell Biology
    • Regenerative Medicine

    Background:

    • The liver possesses remarkable regenerative capabilities following injury.
    • The cellular source of liver regeneration, particularly during impaired hepatocyte proliferation, has been debated.
    • Oval/progenitor cells are traditionally considered key mediators of liver repair.

    Purpose of the Study:

    • To investigate the potential of hepatic stellate cells as progenitor cells in liver regeneration.
    • To clarify the cellular mechanisms underlying the oval/ductular response to liver injury.
    • To explore the plasticity of liver progenitor cell populations.

    Main Methods:

    • Lineage tracing of transplanted rat hepatic stellate cells.
    • Induction of liver damage in host rats.

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  • Analysis of cell contribution to the oval cell response and liver repopulation.

    • Main Results:

    • Transplanted hepatic stellate cells were found to repopulate the damaged rat liver.
    • These stellate cells contributed significantly to the oval cell response.
    • Mesenchymal-derived stellate cells were identified as progenitors for the oval/ductular response in rats.

    Conclusions:

    • Hepatic stellate cells, a mesenchymal cell population, can act as progenitors in the rat liver's oval cell response.
    • The liver exhibits significant cellular plasticity, with multiple cell types capable of contributing to regeneration.
    • Discrepancies in regeneration studies may stem from variations in damage models, injury extent, and species differences.